SEVERE ASTHMA RESEARCH PROGRAM (SARPII) IMAGING CORE

描述(由申请人提供)： 这一辅助RFA建议的总体目标是更好地了解使用多层螺旋CT(MDCT)胸部的成像方式是否可以提供哮喘患者呼吸道重构的非侵入性测量。严重哮喘研究计划(SARPII)的中心假设是，严重哮喘是许多相互作用过程的结果，这些过程不仅导致呼吸道炎症、损伤和修复机制改变，而且存在选定的抗炎过程的失调，这些过程通常调节导致呼吸道重塑的损伤模式。在这项提案中，我们将利用这一独特的资源，这些资源包括预期登记的和仔细描述的重度哮喘患者和适当的对照组(轻度-中度哮喘，正常受试者)。我们建议在SARPII中增加一个成像协议，该协议将包括成像核心(爱荷华大学)、形态核心(华盛顿大学/匹兹堡大学)和生物统计核心(华盛顿大学)。作为这项建议的一部分，受试者将接受胸部多层螺旋CT扫描，然后进行支气管镜检查，并进行引导成像，以指导哪里可以获得支气管内活检，从而对重建的呼吸道进行最佳采样。我们认为，在严重和轻度哮喘的成人受试者(n=200)和正常受试者的特征良好的队列中验证这项技术将提供一种有价值的、临床上有用的、非侵入性的气道重塑测量方法。因此，为了更好地确定与轻度哮喘或正常和疾病对照相比，MDCT胸部是否可以作为一种非侵入性间接测量重度哮喘患者的气道重塑的指标，我们提出了以下目标：1.通过与SARPII研究中的轻度哮喘和正常对照比较，在一组特征良好的重度哮喘受试者中，标准化并评估包括数据采集和图像分析在内的通用成像方案的可靠性。II.调查轻度和重度哮喘患者以及SARPII研究中的正常对照的呼吸道厚度的放射学测量是否与病理和生理指标相关。在轻度和重度哮喘患者和SARPII研究的正常对照组中，研究使用多层螺旋CT成像来前瞻性地确定气道重塑的部位，并通过支气管镜活检指导有针对性的支气管镜评估。呼吸道重塑被认为是导致哮喘患者肺功能长期下降的原因之一。我们认为，评估一种新的成像技术，多层螺旋CT(MDCT)胸部，在一组特征良好的重度和轻度哮喘患者和正常受试者中，将提供一种有价值的、临床有用的、无创性的气道重塑测量方法。这种对呼吸道重塑的测量可能有助于识别哮喘患者，他们可能会发展成严重的疾病，谁可能从早期有针对性的积极治疗中受益。(摘要结束)

DESCRIPTION (provided by applicant): The overall goal of this Ancillary RFA proposal is to better understand whether an imaging modality using multidetector-row CT (MDCT) chest can provide a noninvasive measure of airway remodeling in asthma. The Severe Asthma Research Program's (SARPII) central hypothesis is that severe asthma is a consequence, in part, of numerous interactive processes that lead not only to airway inflammation, injury, and altered repair mechanisms, but that there is dysregulation of selected anti-inflammatory processes that normally modulate the injury pattern leading to airway remodeling. In this proposal, we will utilize this unique resource of prospectively enrolled and carefully characterized subjects with severe asthma and appropriate comparison groups (mild- moderate asthma, normal subjects). We propose to add an Imaging protocol to SARPII that will include an Imaging Core (University of Iowa), Morphology Core (Washington University/University of Pittsburgh), and a Biostats Core (Washington University). As part of this proposal, subjects will undergo MDCT chest then bronchoscopy with guided imaging to direct where endobronchial biopsies can be obtained for the optimal sampling of a remodeled airway. We propose that validating this technology in a well- characterized cohort of adult subjects (n=200) with severe and mild asthma and normal subjects will provide a valuable, clinically useful, noninvasive measure of airway remodeling. Accordingly, in order to better define whether MDCT chest can be used as a noninvasive, indirect measure of airway remodeling in severe asthma in comparison to mild asthma or normal and diseased controls, we propose the following aims: I. Standardize and assess the reliability of a common imaging protocol including both data acquisition and image analysis using MDCT in a well-characterized cohort of subjects with severe asthma in comparison to subjects with mild asthma and normal controls from the SARPII study. II. Investigate whether radiographic measures of airway thickness correlate with pathologic and physiologic markers in subjects with mild and severe asthma and in comparison to normal controls from the SARPII study. III. Investigate the use of imaging with MDCT to prospectively identify sites of airway remodeling and guide targeted bronchoscopic assessment with endobronchial tissue biopsy in subjects with mild and severe asthma and in comparison to normal controls from the SARPII study. Airway remodeling is felt to contribute to the long term decline in lung function that occurs in asthma. We propose that evaluating a new imaging technique, multidetector-row CT (MDCT) chest, in a well-characterized group of subjects with severe and mild asthma and normal subjects will provide a valuable, clinically useful, noninvasive measure of airway remodeling. This measure of airway remodeling may help identify individuals with asthma who are likely to develop severe disease and who may benefit from early targeted, aggressive therapy. (End of Abstract)